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PubMed | University of Medicine and Pharmacy, Cluj-Napoca, The Oncology Institute Prof Dr Ion Chiricuta, National Institute for Research and Development for Biology and Animal Nutrition and The Oncological Institute Prof Dr Ion Chiricuta
Type: | Journal: BMC genomics | Year: 2016

The gastrointestinal tract is the primary site of toxin interaction, an interface between the organism and its surroundings. In this study, we assessed the alteration of intestinal mRNA profile in the case of co-occurrence of zearalenone (ZEA), a secondary Fusarium metabolite, and Escherichia coli (E. coli), on the intestinal porcine epithelial cells IPEC-1. We chose this model since the pig is a species which is susceptible to pathogen and mycotoxin co-exposure.After treating the cells with the two contaminants, either separately or in combination, the differential gene expression between groups was assessed, using the microarray technology. Data analysis identified 1691 upregulated and 797 downregulated genes as a response to E. coli exposure, while for ZEA treated cells, 303 genes were upregulated and 49 downregulated. The co-contamination led to 991 upregulated and 800 downregulated genes. The altered gene expression pattern was further classified into 8 functional groups. In the case of co-exposure to ZEA and E.coli, a clear increase of proinflammatory mechanisms.These results demonstrate the complex effect of single or multiple contaminants exposure at cellular and molecular level, with significant implications that might lead to the activation of pathological mechanisms. A better understanding of the effects of co-contamination is mandatory in developing novel exposure regulations and prevention measures.

Irimie A.I.,University of Medicine and Pharmacy, Cluj-Napoca | Braicu C.,University of Medicine and Pharmacy, Cluj-Napoca | Zanoaga O.,University of Medicine and Pharmacy, Cluj-Napoca | Pileczki V.,University of Medicine and Pharmacy, Cluj-Napoca | And 5 more authors.
OncoTargets and Therapy | Year: 2015

Epigallocatechin-3-gallate (EGCG) is the major bioactive component of green tea. Our experimental data indicated that EGCG treatment suppresses cell proliferation of SSC-4 human oral squamous cell carcinoma (OSCC), the effect being dose- and time-dependent. In parallel was observed the activation of apoptosis and autophagy, in response to EGCG exposure in SSC-4 cells. Treatment with EGCG activates the expression of the BAD, BAK, FAS, IGF1R, WNT11, and ZEB1 genes and inhibits CASP8, MYC, and TP53. All of these results suggest that EGCG has an excellent potential to become a therapeutic compound for patients with OSCC, by inducing tumor cell death via apoptosis and autophagy. © 2015 Irimie et al.

Stanila A.,University of Agricultural Sciences and Veterinary Medicine, Cluj-Napoca | Braicu C.,The Oncology Institute Prof Dr Ion Chiricuta | Stanila S.,University of Agricultural Sciences and Veterinary Medicine, Cluj-Napoca | Pop R.M.,University of Agricultural Sciences and Veterinary Medicine, Cluj-Napoca
Notulae Botanicae Horti Agrobotanici Cluj-Napoca | Year: 2011

The antibacterial properties of differently copper and cobalt amino acids complexes on agar plates was investigated in the present study. The antibacterial activity of amino acid complexes was evaluated against on three bacteria strains (Escherichia coli, Bacillus cereus, Micrococcus luteus). Generally, the amino acids complexes were mainly active against gram-positive organisms, species like Micrococcus luteus being the most susceptible strain tested. It was registered a moderate antibacterial activity against Bacillus cereus. The microorganisms Escherichia coli, which are already known to be multi-resistant to drugs, were also resistant to the amino acids complexes but also to the free salts tested. Escherichia coli were susceptible only to the CoCl2 and copper complex with phenylalanine. The complexes with leucine and histidine seem to be more active than the parent free ligand against one or more bacterial species. Moderate activity was registered in the case of complexes with methionine and phenylalanine. From the complexes tested less efficient antibacterial activity was noted in the case of complexes with lysine and valine. These results show that cobalt and copper complexes have an antibacterial activity and suggest their potential application as antibacterial agents.

Braicu C.,University of Medicine and Pharmacy, Cluj-Napoca | Catana C.,University of Medicine and Pharmacy, Cluj-Napoca | Calin G.A.,University of Houston | Berindan-Neagoe I.,University of Medicine and Pharmacy, Cluj-Napoca | Berindan-Neagoe I.,The Oncology Institute Prof Dr Ion Chiricuta
Current Pharmaceutical Design | Year: 2014

Cancer initiation and progression are governed by a complex multistep process in which successive alterations accumulate in multiple protein-coding and noncoding genes. MicroRNAs are an evolutionarily conserved class of endogenous 19- to 24-nucleotide noncoding RNAs that have been validated as key players in the balance of most cellular processes, including drug resistance. MicroRNAs change the output of protein-coding genes through posttranscriptional regulation by binding in a sequence-specific manner to the transcripts of their target genes. Resistance to therapy remains a major challenge in cancer treatment; clear solutions to this problem have yet to be found, in spite of intensive research in recent years. In this review, we explore the concept of cancer multitherapy using noncoding RNAs. We also address basic scientific questions that are related to personalized cancer treatment. © 2014 Bentham Science Publishers.

PubMed | University of Medicine and Pharmacy, Cluj-Napoca and The Oncology Institute Prof Dr Ion Chiricuta
Type: | Journal: Mediators of inflammation | Year: 2016

Tumors act systemically to sustain cancer progression, affecting the physiological processes in the host and triggering responses in the blood circulating cells. In this study, we explored blood transcriptional patterns of patients with two subtypes of HER2 negative breast cancers, with different prognosis and therapeutic outcome. Peripheral blood samples from seven healthy female donors and 29 women with breast cancer including 14 triple-negative breast cancers and 15 hormone-dependent breast cancers were evaluated by microarray. We also evaluated the stroma in primary tumors. Transcriptional analysis revealed distinct molecular signatures in the blood of HER2- breast cancer patients according to ER/PR status. Our data showed the implication of immune signaling in both breast cancer subtypes with an enrichment of these processes in the blood of TNBC patients. We observed a significant alteration of chemokine signaling, IL-8 signaling, and communication between innate and adaptive immune cells pathways in the blood of TNBC patients correlated with an increased inflammation and necrosis in their primary tumors. Overall, our data indicate that the presence of triple-negative breast cancer is associated with an enrichment of altered systemic immune-related pathways, suggesting that immunotherapy could possibly be synergistic to the chemotherapy, to improve the clinical outcome of these patients.

PubMed | University of Medicine and Pharmacy, Cluj-Napoca, The Oncology Institute Prof Dr Ion Chiricuta and University of Agricultural Sciences and Veterinary Medicine, Cluj-Napoca
Type: Journal Article | Journal: Clujul medical (1957) | Year: 2016

Breast cancer is a heterogeneous disease and the leading cause of cancer mortality worldwide. Triple negative breast cancer (TNBC) is considered to be one of the most aggressive breast neoplasia due to failure of chemotherapy response. Thus, there is an urgent need of finding alternative therapies for TNBC. This study was designed to evaluate the synergistic effect induced by propolis and bee venom on luminal (MCF-7) and TNBC (Hs578T) cell lines.In order to evaluate the synergistic effect of aqueous extract of propolis and bee venom, we treated in combination two breast cancer cell lines: MCF-7(luminal subtype) and Hs578T (TNBC subtype).Our results indicate that both cell lines exhibited similar sensitivity to the aqueous extract of propolis at a dilution of 0.072-0.09 mg/ml. The results concerning IC50 for bee venom on MCF-7 cells was 1 mg/ml, 20 times higher than 0.05 mg/ml in Hs578T cells. By combining the aqueous extract of propolis with bee venom, we obtained synergistic effects at a higher concentration, which was 5 and 2 times stronger than the two treatments alone.Overall, the results from our study indicated that the combination of aqueous extract of propolis and bee venom treatments induced synergistic antiproliferative effects in a concentration-dependent manner in breast cancer cells. Thus we can hypothesize that the combination of honeybee propolis and venom might be involved in signaling pathways that could overcome cells resistance to therapy.

PubMed | University of Medicine and Pharmacy, Cluj-Napoca and The Oncology Institute Prof Dr Ion Chiricuta
Type: Review | Journal: Nutrients | Year: 2016

Colorectal cancer is the third most common cancer in the world and considered to be one of the most diet-related types of cancer. Extensive research has been conducted but still the link between diet and colorectal cancer is complex. Recent studies have highlight microRNAs (miRNAs) as key players in cancer-related pathways in the context of dietary modulation. MicroRNAs are involved in most biological processes related to tumor development and progression; therefore, it is of great interest to understand the underlying mechanisms by which dietary patterns and components influence the expression of these powerful molecules in colorectal cancer. In this review, we discuss relevant dietary patterns in terms of miRNAs modulation in colorectal cancer, as well as bioactive dietary components able to modify gene expression through changes in miRNA expression. Furthermore, we emphasize on protective components such as resveratrol, curcumin, quercetin, -mangostin, omega-3 fatty acids, vitamin D and dietary fiber, with a focus on the molecular mechanisms in the context of prevention and even treatment. In addition, several bioactive dietary components that have the ability to re-sensitize treatment resistant cells are described.

PubMed | University of Medicine and Pharmacy, Cluj-Napoca, the Oncology Institute Prof Dr Ion Chiricuta, Iuliu Hatieganu University of Medicine and Pharmacy and University of Puerto Rico at San Juan
Type: | Journal: OncoTargets and therapy | Year: 2016

Apoptosis is the major downregulated pathway in cancer. Simultaneous inhibition using specific small interfering RNA (siRNA) of two key player genes, p53 and TNF, is an interesting and feasible strategy when it comes to investigating various molecular pathways and biological processes in triple-negative breast cancer (TNBC), which is one of the most aggressive and therapeutically unresponsive forms of breast cancers. Our present research focuses on evaluating the impact of double p53-siRNA and TNF-siRNA knockdown at a cellular level, and also evaluating cell proliferation, apoptosis, induction of autophagy, and gene expression by using reverse transcription polymerase chain reaction array approaches. Simultaneous inhibition of p53 and TNF in Hs578T TNBC human cell line revealed a panel of up- and downregulated genes involved in apoptosis. Furthermore, the effects of double gene knockdown were validated in a second TNBC cell line, MDA-MB-231, by using reverse transcription polymerase chain reaction TaqMan assay. All our findings help in understanding the functional mechanisms of extrinsic apoptosis, cell signaling pathways, and the mechanisms involved in tumor cell survival, growth, and death in TNBC.

PubMed | University of Medicine and Pharmacy, Cluj-Napoca, Albany State University, IMOGEN Research Institute, Babes - Bolyai University and 2 more.
Type: | Journal: PeerJ | Year: 2016

Cancer research is a national and international priority, with the efficiency and effectiveness of current anti-tumor therapies being one of the major challenges with which physicians are faced.To assess the impact of exposure to tobacco smoke, arsenic, and phthalates on cervical cancer treatment.We investigated 37 patients with locally advanced cervical carcinoma who underwent chemotherapy and radiotherapy. We determined cotinine and five phthalate metabolites in urine samples collected prior to cancer treatment, by gas chromatography coupled to mass spectrometry, and urinary total arsenic by atomic absorption spectrometry with hydride generation. We used linear regression to evaluate the effects of cotinine, arsenic, and phthalates on the change in tumor size after treatment, adjusted for confounding variables.We detected no significant associations between urinary cotinine, arsenic, or phthalate monoesters on change in tumor size after treatment, adjusted for urine creatinine, age, baseline tumor size, and cotinine (for arsenic and phthalates). However, higher %mono-ethylhexyl phthalate (%MEHP), a putative indicator of phthalate diester metabolism, was associated with a larger change in tumor size ( = 0.015, 95% CI [0.003-0.03], P = 0.019).We found no statistically significant association between the urinary levels of arsenic, cotinine, and phthalates metabolites and the response to cervical cancer treatment as measured by the change in tumor size. Still, our results suggested that phthalates metabolism may be associated with response to treatment for locally advanced cervical cancer. However, these observations are preliminary and will require confirmation in a larger, more definitive investigation.

PubMed | University of Medicine and Pharmacy, Cluj-Napoca, The Oncology Institute Prof Dr Ion Chiricuta and Dokuz Eylül University
Type: Journal Article | Journal: Molecular and cellular biochemistry | Year: 2016

Ovarian cancer is a highly aggressive pathology, displaying a poor prognosis and chemoresistance to classical therapy. The present study was conducted to evaluate the effect of caffeic acid phenethyl ester (CAPE) on survival of ovarian cancer cell lines, A2780 (sensitive to cisplatin) and A2780cis (resistant to cisplatin). MTT assay was used to evaluate cell viability, while the apoptotic processes were examined by flow cytometry and qRT-PCR. A reduction of cell proliferation and activation of the apoptosis was observed in both cell lines. qRT-PCR evaluation demonstrated the activation of the pro-apoptotic genes (BAD, CASP8, FAS, FADD, p53) in both cell lines. The limited therapeutic effect in A2780 cells is explained by the activation of epithelial-mesenchymal transition-related genes (ZEB1, ZEB2, or TGFBB1) as displayed by Ingenuity Network analysis. Overall data suggest that CAPE can be used as an alternative in sensitizing cells to chemotherapy.

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